Magnetic resonance (MR) imaging is a developing field with ever-expanding applications. Much of this expansion is attributable to the development of a wide array of contrast agents, which increase the contrast of the image by modifying localized areas of the contrast in either a positive or negative maiser. The regions of localization vary considerably among the various types of contrast agents. These regions include specific tissues, organs, cells, antigens, and tumors, as well as the blood pool itself.
Of interest in the present invention are contrast agents used for imaging the blood pool and monitoring its movement. MR imaging assisted by such agents is useful for such procedures as assessments of relative tissue blood volume, estimation of tissue per fusion, and detection of abnormal capillary permeability. Clinical applications include assessments of myocardial and cerebral ischemia, pulmonary embolism, transplants, and neoplasia. To be useful as blood-pool markers, the contrast agents must remain in the pool rather than leaving it through such means as diffusion into extravascular compartments or glomerular filtration. A requisite property of contrast agents is therefore a relatively high molecular weight, generally on the order of 20,000 daltons or more, which prevents the agents from diffusing through normal capillaries and glomerular endothelium. Contrast agents of this type are thus referred to in the art as macromolecular contrast media, or "MMCM." A further advantage of MMCM is that the prolonged intravascular retention of these agents permits imaging of the blood pool in multiple body regions without repeated dosing, thereby eliminating the need for critical timing of the imaging. The enhancement of normal tissues with MMCM 5 minutes after administration, for example, is virtually identical to the enhancement 50 minutes after administration.